Betulinic acid derivatives: a new class of human immunodeficiency virus type 1 specific inhibitors with a new mode of action

J Med Chem. 1996 Mar 1;39(5):1056-68. doi: 10.1021/jm950670t.


A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Betulinic Acid
  • Enzyme Inhibitors / pharmacology
  • HIV-1 / drug effects*
  • HIV-2 / drug effects
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Pentacyclic Triterpenes
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis*
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*
  • Tumor Cells, Cultured


  • Antiviral Agents
  • Enzyme Inhibitors
  • N-(3,30-dihydroxylup-20(29)-en-28-oyl)-11-aminoundecanoic acid
  • N-(3-hydroxy-30-((2'-hydroxyethyl)thio)lup-20(29)-en-28-oyl)-11-aminoundecanoic acid
  • Pentacyclic Triterpenes
  • Reverse Transcriptase Inhibitors
  • Triterpenes
  • betulinylaminoundecanoic acid
  • Betulinic Acid